Dementia is the most common neurological disease in the elderiy. Experimental, epidemiological, and neuropathological evidence suggest associations between vascular factors and cognitive decline and dementia regardless of subtype, with vascular pathology present in half of all dementia cases. However, the mechanisms which underiy these associations are a topic of debate. While large vessel cerebrovascular disease and cortical stroke have been linked to cognitive decline and dementia, the specific role of cerebral small vessel disease is unclear. Few population based studies have assessed cerebral microvascular structure and function in relation to cognitive decline and dementia, due in part to the difficulty of applying specialized and costly imaging techniques in large population based samples. We propose to apply two non- invasive, relatively low cost techniques for assessing microvascular status (with retinal phootography) and function (transcranisal Doppler ultrasound (TCD) with C02 challenge) to test the hypothesis that cerebral hypoperfusion and microvascular disease precede the onset of dementia and contribute to cognitive decline. Because retinal and cerebral arterioles have similar anatomy, physiology and embryology, retinal characteristics assessed by standardized grading of fundus photographs provides a surrogate marker for cerebral microvascular status. Similarly, TCD with C02 challenge is a safe non-invasive technique for assessing cerebral vascular function. Recently, these techniques have been studied in relation to dementia, although the majority of studies have been limited by cross-sectional design, restriction to clinical AD cases, or limited neuropsychological data. Little is known of their associations to eariy cognitive decline and preclinical dementia. Applying these techniques in the EAS will allow us to assess whether retinal microvascular status and cerebrovascular function predict cognitive decline and dementia, with a focus on eariy cognitive changes. To elucidate mechanisms that may underly these associations, we will evaluate whether they mediate associations of vascular risk factors with cognition and will assess the relation of retinal and TCD measures to neuroimaging measures of structual brain changes. RELEVANCE (See instructions): Much is known regarding the prevention and treatment of vascular disease. Better understanding the role of vascular status and function in dementia will direct the application of these strategies toward the prevention of this prevalent condition.